The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

Abstract

The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

Redox Stability Controls the Cellular Uptake and Activity of Ruthenium‐Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)

“…The tissue distribution profile of OCT3 suggests that Ru265 may localize to these tissues. Thus, Ru265 is expected to be a highly valuable tool for studying the role of MCU‐mediated Ca 2+ regulation in diseases related to the heart, brain, and skeletal muscle such as ischemic stroke, neurodegeneration, and cardiovascular disease in vivo …”

Necrosulfonamide Ameliorates Neurological Impairment in Spinal Cord Injury by Improving Antioxidative Capacity

“…In addition to energizing cells, mitochondria also regulate the cell cycle, growth, differentiation, and apoptosis. There is cumulating evidence that mitochondrial dysfunction plays an important role in the progression of CNS diseases such as Parkinson's disease, Alzheimer's disease, cerebral ischemic stroke, Huntington disease, multiple sclerosis, and amyotrophic lateral sclerosis (Liao et al, 2017;Rajda et al, 2017). Furthermore, mitochondrial dysfunction also induces secondary injury and neuronal death after SCI (Beattie et al, 2002;Osellame et al, 2012).…”

Redox Stability Controls the Cellular Uptake and Activity of Ruthenium‐Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)

“…[77][78][79] Thet issue distribution profile of OCT3 suggests that Ru265 may localize to these tissues.Thus, Ru265 is expected to be ahighly valuable tool for studying the role of MCU-mediated Ca 2+ regulation in diseases related to the heart, brain, and skeletal muscle such as ischemic stroke, neurodegeneration, and cardiovascular disease in vivo. [80][81][82] Thestudies above clearly demonstrate that Ru265 is taken up more efficiently than Ru360',d espite being structurally similar. When performing our cellular uptake studies,wewere surprised to find that the cellular uptake of Ru360' was sensitive to the presence of fetal bovine serum (FBS).…”